Publications by authors named "Ehab M Mostafa"

6 Publications

  • Page 1 of 1

Cytotoxic Potential, Metabolic Profiling, and Liposomes of sp. Crude Extract Supported by in silico Analysis.

Int J Nanomedicine 2021 4;16:3861-3874. Epub 2021 Jun 4.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.

Introduction: Sponge- sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable.

Methodology: In the present study, the metabolomic profiling of sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively).

Results: The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds -) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC values ranged from 1.7 to 4.1 µg/mL).

Discussion: Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.
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http://dx.doi.org/10.2147/IJN.S310720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187037PMC
June 2021

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Drug Des Devel Ther 2021 31;15:2325-2337. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Methods: Three semi-synthetic series of compounds (, , and ) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of L. (-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds and showed superior inhibitory activity against EGFR (IC: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds and exhibited the highest cytotoxic activity with average IC values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
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http://dx.doi.org/10.2147/DDDT.S310820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178614PMC
May 2021

Antiulcer Potential of L. cv. Arbequina Leaf Extract Supported by Metabolic Profiling and Molecular Docking.

Antioxidants (Basel) 2021 Apr 22;10(5). Epub 2021 Apr 22.

Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia City, Minia 61111, Egypt.

Gastric ulceration is among the most serious humanpublic health problems. L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of L. cv. Arbequina led to the dereplication of 18 putative compounds (-). In vivo indomethacin-induced gastric ulcer in a rat model was established and the extract was tested at a dose of 300 mg kg compared to cimetidine (100 mg kg). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, HO scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol () and oleacein () can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) ( and , respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.
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http://dx.doi.org/10.3390/antiox10050644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146603PMC
April 2021

Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae : An In-Silico-Supported In-Vitro Study.

Antibiotics (Basel) 2021 Apr 10;10(4). Epub 2021 Apr 10.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae "Sargassaceae" dereplicated eleven compounds -. Further phytochemical investigation afforded two new aryl cresol -, along with eight known compounds -. Both new metabolites, along with showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed and were able to inhibit 5-LOX more preferentially than 15-LOX, while showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes' active sites and explained the varying inhibitory activity for and toward 5-LOX and 15-LOX.
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http://dx.doi.org/10.3390/antibiotics10040416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069941PMC
April 2021

Enhanced full-thickness wound healing via extract delivery based on a chitosan/gelatin dressing incorporating microemulsion.

Drug Dev Ind Pharm 2021 Feb 4;47(2):215-224. Epub 2021 Jan 4.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biological activity in that regard. Genus Sophora is well known to contain flavonoids and phenolic compounds which have antioxidant and inflammatory effects. So, the aim of the current study was to develop and evaluate chitosan/gelatin based extract-loaded microemulsion as wound dressing. extract (SGE) contained 16 major compounds which have reasonable antioxidant activity. The developed microemulsion showed that Tween 80 produced significant ( < 0.05) lower particle size than Pluronic F127 at the same SGE concentration whereas high concentration of extract results in large particle size. Thermodynamic stability studies showed that using higher concentration of the extract produced less stable formulations. The selected formulation was impregnated in the dressing base (chitosan/gelatin; 2:1 w/w ratio) which exhibited more water absorption. evaluation revealed that the dressing displayed superior wound repair compared to the control in terms histological examination and determination of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Thus, SGE-loaded microemulsion-impregnated gelatin/chitosan could be a potential candidate for the wound healing.
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http://dx.doi.org/10.1080/03639045.2020.1863420DOI Listing
February 2021

Soy isoflavone-loaded alginate microspheres in thermosensitive gel base: attempts to improve wound-healing efficacy.

J Pharm Pharmacol 2019 May 14;71(5):774-787. Epub 2019 Jan 14.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.

Objectives: This study aims to develop thermosensitive gel containing soy isoflavone (antioxidant and anti-inflammatory natural agent) alginate microspheres for enhancement of wound-healing performance.

Methods: Soy isoflavone microspheres were prepared by ionic cross-linking method and optimized using the Box-Behnken optimization design. Formulations were characterized in terms of particle size, encapsulation efficiency and equilibrium swelling degree. The optimized formula was incorporated in Pluronic F127 gel base and examined for in vivo wound-healing efficacy.

Key Findings: Results showed mean particle size between 18 and 25 μm, encapsulation efficiency of over 75% and equilibrium swelling degree over 1.9. Thermal analysis indicated interaction between alginate and CaCl and embedding of soy isoflavone in microspheres. In vivo wound-healing efficacy showed significant advance in re-epithelization, mature collagen synthesis and proangiogenesis. Immunohistochemical investigation exhibited promising alpha-smooth muscle actin immunopositive cells expression, fibroblast activation and expression of proliferating cell nuclear antigen (proliferation marker) in the epidermis and in the dermis.

Conclusions: The developed formulation would appear to be a promising topical preparation for accelerating healing process.
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http://dx.doi.org/10.1111/jphp.13066DOI Listing
May 2019
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